Wnt-β-catenin signaling pathway inhibition by sclerostin may protect against degradation in healthy but not osteoarthritic cartilage

• Published in: Molecular medicine reports Vol. 15; no. 5; pp. 2423 - 2432
• Main Authors: Wu, Jiang, Ma, Long, Wu, Long, Jin, Qunhua
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.05.2017; Spandidos Publications UK Ltd
• Subjects: ADAMTS4 Protein - genetics; ADAMTS4 Protein - metabolism; Adult; Aged; Antigens; beta Catenin - genetics; beta Catenin - metabolism; Bone Morphogenetic Proteins - pharmacology; cartilage; Cartilage (articular); Cartilage diseases; Cartilage, Articular - metabolism; Cell adhesion & migration; Cells, Cultured; Chondrocytes; Chondrocytes - cytology; Chondrocytes - drug effects; Chondrocytes - metabolism; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Female; Genetic Markers; Humans; Immunohistochemistry; Interleukin 1; Interleukin-1alpha - pharmacology; Joint surgery; Knee - pathology; Low Density Lipoprotein Receptor-Related Protein-5 - genetics; Low Density Lipoprotein Receptor-Related Protein-5 - metabolism; Low Density Lipoprotein Receptor-Related Protein-6 - genetics; Low Density Lipoprotein Receptor-Related Protein-6 - metabolism; Male; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; Middle Aged; Osteoarthritis; Osteoarthritis - metabolism; Osteoarthritis - pathology; Osteocytes; Polymerase chain reaction; Reverse transcription; sclerostin; Signal transduction; SOST protein; Studies; therapy; Transcription factors; Western blotting; Wnt protein; Wnt Signaling Pathway - drug effects; Wnt-β-catenin; Young Adult; β-catenin; China
• ISSN: 1791-2997; 1791-3004; 1791-3004
• DOI: 10.3892/mmr.2017.6278

The aim of the present study was to determine the regulation of sclerostin (SOST) in osteoarthritis (OA) and its effect on articular cartilage degradation. Human cartilage samples from healthy and OA subjects were assessed by Safranin O staining and immunohistochemistry. Primary chondrocytes were pre-incubated with 250 ng/ml SOST, 10 ng/ml interleukin-1-α (IL-1α) or a combination of the two. The effects of treatment on the Wnt-β-catenin signaling pathway and cartilage degradation were examined by reverse transcription-quantitative polymerase chain reaction and western blotting. SOST was detected in the cartilage focal area, demonstrating secretion by osteocytes and chondrocytes. SOST has been identified to inhibit the Wnt-β-catenin signaling pathway by binding to low-density lipoprotein-related receptors 5 and 6, and catabolic factors were decreased in healthy chondrocytes. However, SOST did not influence human OA chondrocytes. IL-1α activated the Wnt-β-catenin signaling pathway and promoted cartilage degradation, which was inhibited by SOST in healthy and OA cartilage. The results of the present study suggested that SOST is important in maintaining the integrity of healthy, but not end-stage OA, cartilage.